Self-expanding device for the gastrointestinal or urogenital area

ABSTRACT

Devices for treatments of diseases and disorders associated with the gastrointestinal tract, especially the stomach, or urinogenital tract are described herein. Initially, the device is in a temporary form which is suitable for oral or rectal administration. After exposure to a stimulus, such as a temperature or pH change, the device changes shape to a permanent form, which allows it to become mechanically fixed in the stomach, esophagus or intestine. In one embodiment, the device is used to reduce the volume of the stomach, esophagus or intestine without interfering with the flow of the food through the gastrointestinal tract. The device may be used to help overweight patients lose weight and to deliver drugs to treat disorders and diseases in the in the stomach or intestine. The devices are manufactured from a stimuli-sensitive polymeric material, which is biocompatible and primarily adapted to the mechanical properties and geometry in the area to which it is applied. In the preferred embodiment, the material is a shape memory polymer. Depending on the desired application, the polymer may be either biodegradable or non-degradable.

FIELD OF THE INVENTION

The present invention relates to devices to treat diseases and disordersassociated with the gastrointestinal or urinogenital area.

BACKGROUND OF THE INVENTION

The transit time through the gastrointestinal (GI) tract often limitsthe amount of drug available for absorption at its most efficientabsorption site, or for local activity at one segment of the GI tract.The latter is particularly true when the absorption site is high in theGI tract, for example, when the required treatment is local in thestomach as is often the case with ulcers.

A number of different patents describe oral compositions for increasingthe time that the drug is delivered to the stomach. U.S. Pat. No.4,451,260 to Mitra discloses orally administered, sustained release,flexible medicament devices which are formed from multilayer composites.These devices float in the stomach.

U.S. Pat. Nos. 4,735,804; 4,758,436; and 4,767,627 to Caldwell et al.disclose drug delivery devices that contain a polymeric, shaped solidthat is retained in the stomach. The device is compressed for oraldelivery, expands in the stomach to size that prevents passage through apylorus, and then erodes over time in the presence of gastric juices.U.S. Pat. No. 5,007,790 to Shell describes as oral drug dosage form thatswells upon delivery to the stomach so that it resides in the stomachand provides prolonged drug delivery. The drug is presented to thegastric mucosa as a solution, rather than in a solid state. U.S. Pat.No. 5,972,389 to Sheel discloses swellable polymer systems designed todeliver sparingly soluble or insoluble drugs into the gastrointestinaltract as a result of the gradual erosion of the polymer.

These compositions cannot be specifically designed to treat a variety ofdiseases and disorders.

Therefore it is an object of the invention to provide devices that canbe tailored to treat different diseases and disorders of thegastrointestinal tract.

It is a further object of the invention to provide devices that can beeasily removed from the gastrointestinal tract.

BRIEF SUMMARY OF THE INVENTION

Devices for treatments of diseases and disorders associated with thegastrointestinal tract, especially the stomach, or urinogenital tracthave been developed. Initially, the device is in a temporary form whichis suitable for oral or intraluminal administration. After exposure to astimulus, such as a temperature or pH change, the device changes shapeto a permanent form, which allows it to become mechanically fixed in thestomach, esophagus or intestine. In one embodiment, the device is usedto reduce the volume of the stomach, esophagus or intestine withoutinterfering with the flow of the food through the gastrointestinaltract. The device may be used to help overweight patients lose weightand to deliver drugs to treat disorders and diseases in the in thestomach or intestine. The devices are manufactured from astimuli-sensitive polymeric material, which is biocompatible andprimarily adapted to the mechanical properties and geometry in the areato which it is applied. In the preferred embodiment, the material is ashape memory polymer. Depending on the desired application, the polymermay be either biodegradable or non-degradable.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a drawing of devices in their permanent forms.

FIG. 2 is a drawing of devices in their temporary forms. The temporaryform may be compressed or elongated.

DETAILED DESCRIPTION OF THE INVENTION

I. Devices

Devices for treatments of diseases and disorders associated with thegastrointestinal tract or urogenital region are described herein. Thedevice has a form which allows it to become fixed mechanically, forexample, either in the stomach, esophagus or intestine. The device ismanufactured from a stimuli-sensitive polymeric material, which isbiocompatible and primarily adapted to the mechanical properties andgeometry in the area to which it is applied. In the preferredembodiment, the material is a shape-memory-polymer.

The device is capable of changing from one form to another form based onthe presence of a stimulus. The stimulus may be a change in temperatureor pH, or the presence/absence of water or light. The first form isreferred to herein as the “temporary form”. The second form is referredto herein as the “permanent form”.

Different types of polymers respond to different stimuli. When thedevice is exposed to the appropriate stimulus, it changes shape (hereinreferred to as the “shape memory effect”). The shape memory effect isthe transition from the temporary form to the permanent form. Suitablestimuli for activating the shape memory effect include: (1) an increasein temperature, (2) a change in the pH, (3) the application of light,and (4) the presence of water. The pH stimulus may be a change from a pHgreater than 7 to one that is less than 7, such as occurs upon entryinto the stomach. Alternatively, the pH stimulus may be from a pH thatis less than 7 to one that is greater than 7, such as occurs upon entryinto the intestine. Light may increase the temperature of theenvironment. Alternatively, light may catalyze a photosensitve orphotochemical reaction in the material that forms the device. Thepresence of water may cause the device to swell and/or may increasediffusion of materials.

A. Shape Memory Polymers

Shape memory polymers (SMP) respond to a shape memory effect. Shapememory polymers are described in U.S. Pat. No. 6,160,084 to Langer etal., and U.S. Pat. No. 6,388,043 to Robert S. Langer and AndreasLendlein, the disclosures of which are incorporated herein by reference.

SMPs are generally characterized as having netpoints and flexiblesegments. These netpoints can be chemical or physical in nature. SMPsare characterized as phase segregated linear block co-polymers having ahard segment and a soft segment. The hard segment is typicallycrystalline, with a defined melting point, and the soft segment istypically amorphous, with a defined glass transition temperature. Insome embodiments, however, the hard segment is amorphous and has a glasstransition temperature rather than a melting point. In otherembodiments, the soft segment is crystalline and has a melting pointrather than a glass transition temperature of the hard segment.

When the SMP is heated above the melting point or glass transitiontemperature of the hard segment, the material can be shaped. Thispermanent or original shape can be memorized by cooling the SMP belowthe melting point or glass transition temperature of the hard segment.When the shaped SMP is cooled below the melting point or glasstransition temperature of the soft segment white the shape is deformed,a new (temporary) shape is fixed. The original shape is recovered byheating the material above the melting point or glass transitiontemperature of the soft segment but below the melting point or glasstransition temperature of the hard segment. In another method forsetting a temporary shape, the material is deformed at a temperaturelower than the melting point or glass transition temperature of the softsegment, resulting in stress and strain being absorbed by the softsegment. When the material is heated above the melting point or glasstransition temperature of the soft segment, but below the melting point(or glass transition temperature) of the hard segment, the stresses andstrains are relieved and the material returns to its original shape. Therecovery of the original shape, which is induced by an increase intemperature, is called the thermal shape memory effect. Properties thatdescribe the shape memory capabilities of a material are the shaperecovery of the original shape and the shape fixity of the temporaryshape.

Several physical properties of SMPs other than the ability to memorizeshape are significantly altered in response to external changes intemperature and stress, particularly at the melting point or glasstransition temperature of the soft segment. These properties include theelastic modulus, hardness, flexibility, vapor permeability, damping,index of refraction, and dielectric constant. The elastic modulus (theratio of the stress in a body to the corresponding strain) of an SMP canchange by a factor of up to 200 when heated above the melting point orglass transition temperature of the soft segment. Also, the hardness ofthe material changes dramatically when the soft segment is at or aboveits melting point or glass transition temperature. When the material isheated to a temperature above the melting point or glass transitiontemperature of the soft segment, the damping ability can be up to fivetimes higher than a conventional rubber product. The material canreadily recover to its original molded shape following numerous thermalcycles, and can be heated above the melting point of the hard segmentand reshaped and cooled to fix a new original shape.

Preferred SMPs can hold more than one shape in memory. For example, thecomposition can include a hard segment and at least two soft segments.The T_(trans) of the hard segment is at least 10° C., and preferably 20°C., higher than the T_(trans) of one of the soft segments, and theT_(trans) of each subsequent soft segment is at least 10° C., andpreferably 20° C., lower than the T_(trans) of the preceding softsegment. A multiblock copolymer with a hard segment with a relativelyhigh T_(trans) and a soft segment with a relatively low T_(trans) can bemixed or blended with a second multiblock copolymer with a hard segmentwith a relatively low T_(trans) and the same soft segment as that in thefirst multiblock copolymer. Since the soft segments in both multiblockcopolymers are identical, the polymers are miscible in each other whenthe soft segments are melted. The resulting blend has three transitiontemperatures: one for the first hard segment, one for the second hardsegment, and one for the soft segment. Accordingly, these materials areable to memorize two different shapes.

The hard segments can be linear oligomers or polymers, and can be cycliccompounds, such as crown ethers, cyclic di-, tri-, or oligopetides, andcyclic oligo (ester amides).

The physical interaction between hard segments can be based on chargetransfer complexes, hydrogen bonds, or other interactions, since somesegments have melting temperatures that are higher than the degradationtemperature. In these cases, there is no melting or glass transitiontemperature for the segment. A non-thermal mechanism, such as a solvent,is required to change the segment bonding.

The segments preferably are oligomers. As used herein; the term“oligomers” refers to a linear chain molecule having a molecular weightup to 15,000 Da. The ratio by weight of the hard segment: soft segmentsis between about 5:95 and 95:5, preferably between 20:80 and 80:20.

The polymers are selected based on the desired glass transitiontemperature(s) (if at least one segment is amorphous) or the meltingpoint(s) (if at least one segment is crystalline), which in turn isbased on the desired applications, taking into consideration theenvironment of use. Preferably, the number average molecular weight ofthe polymer block is greater than 400, and is preferably in the range ofbetween 500 and 15,000.

The transition temperature at which the polymer abruptly becomes softand deforms can be controlled by changing the monomer composition andthe kind of monomer, which enables one to adjust the shape memory effectat a desired temperature.

The thermal properties of the polymers can be detected for example, bydynamic mechanical thermoanalysis or differential scanning calorimetry(DSC) studies. In addition the melting point can be determined using astandard mp apparatus.

The polymers can be thermoset or thermoplastic polymers, althoughthermoplastic polymers may be preferred due to their ease of molding.

Preferably, the degree of crystallinity of the polymer or polymericblock(s) is between 3 and 80%, more preferably between 3 and 60%. Whenthe degree of crystalinity is greater than 80% while all soft segmentsare amorphous, the resulting polymer composition has poor shape memorycharacteristics.

The tensile modulus of the polymers below the T_(trans) is typicallybetween 50 MPa and 2 GPa (gigapascals), whereas the tensile modulus ofthe polymers above the T_(trans) is typically between 1 and 500 MPa.Preferably, the ratio of elastic modulus above and below the T_(trans)is 20 or more. The higher the ratio, the better the shape memory of theresulting polymer composition.

The polymer segments can be natural or synthetic, although syntheticpolymers are preferred. The polymer segments can be biodegradable ornon-biodegradable, although the resulting SMP composition isbiodegradable. As used herein, the term “biodegradable” typically refersto materials that are bioresorbable and/or degrade and/or break down bymechanical degradation upon interaction with a physiological environmentinto components that are metabolizable or excretable, over a period oftime from minutes to three years, preferably less than one year, whilemaintaining the requisite structural integrity. In general,biodegradable materials degrade by hydrolysis, by exposure to water orenzymes under physiological conditions, by surface erosion, bulkerosion, or a combination thereof. Non-biodegradable polymers used formedical applications preferably do not include aromatic groups, otherthan those present in naturally occurring amino acids.

Representative natural polymer segments or polymers include proteinssuch as zein, modified zein, casein, gelatin, gluten, serum albumin, andcollagen, and polysaccharides such as alginate, celluloses, dextrans,pullulane, and polyhyaluronic acid, as well as chitin,poly(3-hydroxyalkanoate)s, especially poly(β-hydroxybutyrate),poly(3-hydroxyoctanoate) and poly(3-hydroxyfatty acids).

Representative natural biodegradable polymer segments or polymersinclude polysaccharides such as alginate, dextran, cellulose, collagen,and chemical derivatives thereof (substitutions, additions of chemicalgroups, for example, alkyl, alkylene, hydroxylations, oxidations, andother modifications routinely made by those skilled in the art), andproteins such as albumin, zein and copolymers and blends thereof, aloneor in combination with synthetic polymers.

Representative synthetic polymer blocks include polyphosphazenes,poly(vinyl alcohols), polyamides, polyester amides, poly(amino acid)s,synthetic poly(amino acids), polyanhydrides, polycarbonates,polyacrylates, polyalkylenes, polyacrylamides, polyalkylene glycols,polyalkylene oxides, polyalkylene terephthalates, polyortho esterspolyvinyl ethers, polyvinyl esters, polyvinyl halides,polyvinylpyrrolidone, polyesters, polylactides, polyglycolides,polysiloxanes, polyurethanes and copolymers thereof.

Examples of suitable polyacrylates include poly(methyl methacrylate),poly(butyl methacrylate), poly(isobutyl methacrylate), poly(hexylmethacrylate), poly(isodecyl methacrylate), poly(lauryl methacrylate),poly(phenyl methacrylate), poly(methyl acrylate), poly(isopropylacrylate), poly(isobutyl acrylate) and poly(octadecyl acrylate).

Synthetically modified natural polymers include cellulose derivativessuch as alkyl celluloses, hydroxyalkyl celluloses, cellulose ethers,cellulose esters, nitrocelluloses, and chitosan. Examples of suitablecellulose derivatives include methyl cellulose, ethyl cellulose,hydroxypropyl cellulose, hydroxyporpyl methyl cellulose, hydroxybutylmethyl cellulose, cellulose acetate, cellulose propionate, celluloseacetate butyrate, cellulose acetate phthalate, carboxymethyl cellulose,cellulose triacetate and cellulose sulfate sodium salt. These arecollectively referred to herein as “celluloses”.

Representative synthetic degradable polymer segments or polymers includepolyhydroxy acids, such as polylactides, polyglycolides and copolymersthereof; poly(ethylene terephthalate); polyhydroxybutyric acid);poly(hydroxyvaleric acid); poly([lactide-co-(ε-caprolactone)];poly[glycolide-co-(ε-caprolactone)]; polycarbonates, poly(pseudo aminoacids); poly(amino acids); poly(hydroxyalkanoate)s; polyanhydrides;polyortho esters; and blends and copolymers thereof.

Examples of non-biodegradable polymer segments or polymers includeethylene vinyl acetate, poly(meth)acrylic acid, polyamides,polyethylene, polypropylene, polystyrene, polyvinyl chloride,polyvinylphenol, and copolymers and mixtures thereof.

Rapidly bioerodible polymers such as poly(lactide-co-glycolide)s,polyanhydrides, and polyorthoesters, which have carboxylic groupsexposed on the external surface as the smooth surface of the polymererodes, also can be used. In addition, polymers containing labile bonds,such as polyanhydrides and polyesters, are well known for theirhydrolytic reactivity. Their hydrolytic degradation rates can generallybe altered by simple changes in the polymer backbone and their sequencestructure.

Various polymers, such as polyacetylene and polypyrrole, are conductingpolymers. These materials are particularly preferred for uses in whichelectrical conductance is important. Examples of these uses includetissue engineering and any biomedical application where cell growth isto be stimulated. These materials may find particular utility in thefield of computer science, as they are able to absorb heat withoutincreasing in temperature better than SMAs. Conducting shape memorypolymers are useful in the field of tissue engineering to stimulate thegrowth of tissue, for example, nerve tissue.

Shape memory polymers that are generally usable include crystallinepolyolefin crosslinked substances, crystalline trans-isoprenecrosslinked substances, crystalline trans-polybutadiene crosslinkedsubstances, polynorbornene, poly(vinylchloride), poly(methylmethacrylate), polycarbonate, acrylonitrile-butadiene (AB) resin,polyethers, polyamides, polysiloxanes, polyurethanes, polyether amides,polyurethane/ureas, polyether esters, and urethane/butadiene copolymers.

The shape memory effect can also be triggered by contact of the shapememory polymer (SMP) with water. This SMP is characterized by a glasstransition temperature and is preferably amorphous. The programming ofthe SMP can be carried out using standard thermal shape memory. Thepolymer is able to absorb a certain amount of water like a hydrogel,however, the resulting degree of swelling is smaller, for example, theweight of the SMP increases about 0.5 to 4 wt %. Compared to a hydrogel,the mechanical properties of this slightly swollen: material are mainlylike the, bulk material (non-swollen). The absorption of water leads toa decrease in glass transition temperature of about 10 to 30 K(softening effect). Therefore, a glass transition temperature which wasoriginally above body temperature can be decreased to below bodytemperature. When such an SMP is used at body temperature, in thestomach, for example, the shape memory effect will be activated (bywater absorption). The swelling of the SMP occurs preferably within 20to 90 minutes and should correspond with the residence time of the SMPdevice in the stomach, which is, typically 2 to 4 hours.

In addition, the swelling of the SMP can be altered by adjusting the pHand/or by coating the SMP with a pH-sensitive material so that swellingonly occurs at certain pH ranges. For example, pH-sensitive coatings,which are well-known in the pharmaceutical industry; can be used toallow swelling of the SMP only at a lower pH, for applications in thestomach, or at a higher pH, for applications in the intestinal tract.Thus, pH-sensitive coatings can be used to prevent swelling of the SMPin the esophagus when, delivered orally.

Typically the pH-sensitive materials are insoluble solids in neutral oracidic aqueous solutions, and then they dissolve (or degrade anddissolve) as the pH of the solution rises above a pH value ranging from3 to 9, preferably 6 to 8. Exemplary pH-sensitive materials includepolyacrylamides, phthalate derivatives (i.e., compounds with covalentlyattached phthalate moleties) such as acid phthalates of carbohydrates,amylose acetate phthalate, cellulose acetate phthalate, other celluloseester phthalates, cellulose ether phthalates, hydroxypropyl cellulosephthalate, hydroxypropyl ethylcellulose phthalate, hydroxypropyl methylcellulose phthalate, methyl cellulose phthalate, polyvinyl acetatephthalate, polyvinyl acetate hydrogen phthalate, sodium celluloseacetate phthalate, starch acid phthalate, styrene-maleic acid dibutylphthalate copolymer, styrene-maleic acid polyvinyl acetate phthalatecopolymer, styrene and maleic acid copolymers, formalized gelatin,gluten, shellac, salol, keratin, keratin sandarac-tolu, ammoniatedshellac, benzophenyl salicylate, cellulose acetate trimellitate,cellulose acetate blended with shellac, hydroxypropylmethyl celluloseacetate succinate, oxidized cellulose, polyacrylic acid derivatives suchas acrylic acid and acrylic ester copolymers, methacrylic acid andesters thereof, vinyl acetate and crotonic acid copolymers.

Preferred pH-sensitive materials include shellac; phthalate derivatives,particularly cellulose acetate phthalate, polyvinyl acetate phthalateand hydroxypropyl methylcellulose phthalate; polyacrylic acidderivatives, particularly polymethyl methacrylate blended with acrylicacid and acrylic ester copolymers; and vinyl acetate and crotonic acidcopolymers.

The pH-sensitive material is preferably blended with an inertnon-dissolving material. By inert is meant a material that is notsubstantially affected by a change in pH in the triggering range. Byaltering the proportion of a pH-sensitive material to inertnon-dissolving material the time lag subsequent to triggering and priorto release may be tailored. For example, for capsule devices, the blendof pH-sensitive material to inert non-dissolving material may betailored to control the time when the capsule halves separate afterbeing triggered. Thus, preferably a proportional mixture of pH-sensitivematerial to inert nondissolving material is used that provides thedesired release time lag subsequent to triggering. Any inertnon-dissolving material may be used that does not react with thetrigger. Typically, increasing the proportion of inert nondissolvingmaterial will lengthen the time lag after triggering and subsequent torelease of the beneficial agent. Preferably, the inert material isselected from the list of materials given for the semipermeable membrane(above).

Alternatively pH-sensitive materials can be used that are insolublesolids in neutral or alkaline solutions, and then they dissolve (ordegrade and dissolve) as the pH of the solution drops below a pH valueranging from 3 to 9. Exemplary pH-sensitive materials include copolymersof acrylate polymers with amino substituents and acrylic acid esters.Additional pH-sensitive materials include polyfunctional polymerscontaining multiple groups that become ionized as the pH drops belowtheir pKa. A sufficient quantity of these ionizable groups must beincorporated in the polymer such that in aqueous solutions having a pHbelow the pKa of the ionizable groups, the polymer dissolves. Theseionizable groups can be incorporated into polymers as block copolymers,or can be pendent groups attached to a polymer backbone, or can be aportion of a material used to crosslink or connect polymer chains.Examples of such ionizable groups include polyphosphene, vinyl pyridine,vinyl aniline, polylysine, polyornithine, other proteins, and polymerswith substituents containing amino moieties.

In one embodiment, the programmable SMP has a thermal shape memory andis able to swell in an aqueous medium like a hydrogel. The polymer mayoptionally be ionically cross-linked with multivalent ions or polymers.When the programmed polymer swells, the physical crosslinks disappearand trigger the shape memory effect. In contrast to hydrogels, the shapechanges and the volume increases in the SMP.

In another embodiment, the swelling of the SMP can be adjusted byaltering the pH, and in a preferred embodiment, the SMP comprises a pHsensitive coating which allows swelling only at specific pH ranges.

The polymer may also be in the form of a hydrogel (typically absorbingup to about 90% by weight of water), and can optionally be ionicallycrosslinked with multivalent ions or polymers. Ionic crosslinkingbetween soft segments can be used to hold a structure, which whendeformed, can be reformed by breaking the ionic crosslinks between thesoft segments. The polymer may also be in the form of a gel in solventsother than water or aqueous solutions. In these polymers, the temporaryshape can be fixed by hydrophilic interactions between soft segments.

Hydrogels can be formed from polyethylene glycol, polyethylene oxide,polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylates, poly(ethyleneterephthalate), poly(vinyl acetate), and copolymers and blends thereof.Several polymeric segments, for example, acrylic acid, are elastomericonly when the polymer is hydrated and hydrogels are formed. Otherpolymeric segments, for example, methacrylic acid, are crystalline andcapable of melting even when the polymers are not hydrated. Either typeof polymeric block can be used, depending on the desired application andconditions of use.

For example, shape memory is observed for acrylic acid copolymers onlyin the hydrogel state, because of the acrylic acid units aresubstantially hydrated and behave like a soft elastomer with a very lowglass transition temperature. The dry polymers are not shape memorypolymers. When dry, the acrylic acid units behave as a hard plastic evenabove the glass transition temperature and show no abrupt change inmechanical properties on heating. In contrast, copolymers includingmethyl acrylate polymeric segments as the soft segments show shapememory properties even when dry.

The polymers can be obtained from commercial sources such as SigmaChemical Co., St. Louis, Mo.; Polysciences, Warrenton, Pa.; AldrichChemical Co., Milwaukee, Wis.; Fluka, Ronkonkoma, N.Y.; and BioRad,Richmond, Calif. Alternately, the polymers can be synthesized frommonomers obtained from commercial sources, using standard techniques.

B. Forms of the Devices

In the temporary form, the device is fixed in a compressed or stretchedshape due to the shape memory effect of the matrix material (see FIG.2). The shape of the device in its temporary form is selected so thatthe device is suitable for swallowing by a patient or for rectal orurinogenital administration. In this situation, the shape will bedetermined by the application, for example, for gastric reduction, thesize of the device will be based on how much stomach is to be filled bythe device.

After exposure to the stimulus, the device changes to a permanent form(see FIG. 1). The permanent form fixes mechanically in the stomach,esophagus or intestine. In the preferred embodiment, the device is usedfor gastric reduction. The device reduces the volume of the stomach,esophagus or intestine without interfering with the flow of the foodthrough the gastrointestinal tract. The reduction in volume may be greator small. For example, in the case of an anorectic device which is usedto assist in weight loss, a large volume of the stomach should be filledwith the device. In contrast, when the device serves as a drug depot,delivery device for biologically active agents, or as a protectivecoating, the reduction in the volume in the stomach, esophagus orintestine should be minimal. Overweight patients can use the device tolose weight. The device fills the stomach thereby reducing the capacityof the stomach for food and the feeling of hunger.

In another embodiment, the device is a matrix used in the treatment ofgastritis. The matrix lines the stomach's septum and thereby protectsthe stomach against the contents or juice of the stomach for a discreteperiod of time.

1. Drug Delivery

For drug delivery, device may be in the form of a pill or capsule (seeFIG. 2). Alternatively, the device may be incorporated in a capsule.However, in this embodiment, the capsule does not serve as the temporaryform. Typically, the device is loaded with one or more biologicallyactive agents, including drugs, prophylactics or diagnostic oranalytical agents (e.g. contrast medium). These may be organiccompounds, proteins or peptides, sugars or carbohydrates, nucleic acids,lipids, or combinations thereof. The material of the device can bebiodegradable or non-biodegradable. Optionally, the device is coated toimprove its shelf-life, increase slippage for swallowing, or improve thegeneral infiltration into the stomach or intestine, or alter releasecharacteristics.

In one embodiment, the device is a matrix that forms a stent-like devicein the esophagus. The matrix may contain one or more biologically activeagents, such as drugs. For example, the drug may be effective in thetreatment of pyrosis.

2. Urogenital Devices

The device may be suitable for administration to the urinogenital tract.Optionally, the device contains one or more biologically active agents.In one embodiment, the device acts as a contraceptive. For urogenitalapplications, for example, for contraception or drug delivery in theuterus, the device will be shaped for ease of insertion into the vaginaor cervix, where it enlarges or alters shape so that it is retained. Forbladder disorders, such as reflux or incontinence, the device is shapedso that it can be safely positioned at a point where additionalretention is desired, such as the point at which the ureter connects tothe bladder.

C. Biologically Active Agents

The device may contain one or more biologically active agents, such asdrugs and diagnostic agents, which are effective at treating disordersand diseases in the gastrointestinal tract. The term “drug” refers toany pharmaceutically active substance capable of being administered in aparticulate formulation, which achieves the desired effect. Drugs can besynthetic or natural organic compounds, proteins or peptides,oligonucleotides or nucleotides, or polysaccharides or sugars. Drugs mayhave any of a variety of activities, which may be inhibitory orstimulatory, such as antibiotic activity, antiviral activity, antifungalactivity, steroidal activity, cytotoxic or anti-proliferative activity,anti-inflammatory activity, analgesic or anesthetic activity, or beuseful as contrast or other diagnostic agents. A description of classesof drugs and species within each class can be found in Martindale, TheExtra Pharmacopoeia, 31^(st) Ed., The Pharmaceutical Press, London(1996) and Goodman and Gilman, The Pharmacological Basis ofTherapeutics, (9^(th) Ed., McGraw-Hill Publishing company (1996)). In apreferred embodiment, the agent is suitable for treating disorders anddiseases in the stomach or intestine, including but not limited togastritis, gastroparesis, peptic ulcers, Menetrier's disease and gastricand colorectal cancer. In another embodiment, the agent is used fortreatment of urogenital infections and disorders including but notlimited to bacterial vaginosis, trichomoniasis, candidiasis, ovariancancer, vaginal cancer, cervical cancer, prostate cancer, bladdercancer, kidney cancer, vulvar cancer, uterine cancer, urinary tractinfections, and incontinence. Finally, the agent may also be used forcontraception.

II. Methods of Making the Devices

The devices can be formed by standard techniques to mold, cast or shapethe device.

The devices can be prepared using shape memory polymers. In oneembodiment, the SMP contains a hard segment, a first soft segment, and asecond soft segment, where the first soft segment has a T_(trans) atleast 10° C. below that of the hard segment and at least 10° C. abovethat of the second soft segment. After the composition is shaped at atemperature above the T_(trans) of the hard segment it can be cooled toa temperature below that of the T_(trans) of the first soft segment andabove that of the second soft segment and formed into a second shape.The composition can be formed into a third shape after it has beencooled below the T_(trans) of the second soft segment. The compositioncan be heated above the second soft segment to return the composition tothe second shape. The composition can be heated above the T_(trans) ofthe first soft segment to return the composition to the first shape. Thecomposition can also be heated above the T_(trans) of the hard segment,at which point the composition loses the memory of the first and secondshapes and can be reshaped using the method described above.

III. Methods of Using the Devices

The device can be delivered orally to a patient for delivery to thegastrointestinal tract. Alternatively, the device can be administeredrectally for treatment of the gastrointestinal tract. Typically thedevice would be administered through the vagina or ureter to theurinogenital tract. One or several devices can be applied at the sametime. After the device has remained at the site in the gastrointestinaltract for the prescribed period of time, it is expelled from the site.

In one embodiment, the material is hydrolytically or enzymaticallydegradable within a predetermined period of time. Soluble products ofdecomposition or intestine moving particles are then secreted.

In a second embodiment, the material returns to the first temporary formor to a second programmed temporary form, which is so small that thedevice is not longer mechanically fixed to the site and the device issecreted. Stimuli for the transition from the permanent form: to thefirst or a second temporary form include: (1) a change in temperature,(2) a substance that delivers the stimuli by taking it at any point oftime, (3) light, e.g. ultraviolet or infrared, and (4) ultrasound.

It is understood that the disclosed invention is not limited to theparticular methodology, protocols, and reagents described as these mayvary. It is also to be understood that the terminology used herein isfor the purpose of describing particular embodiments only and is notintended to limit the scope of the present invention which will belimited only by the appended claims.

1. A device to treat diseases and disorders of the gastrointestinal orurinogenital tract comprising a shape memory polymer having a firsttemporary form allowing the device to be inserted and a second permanentform to retain the device within the gastrointestinal or urogenitaltract.
 2. The device in claim 1, further comprising a biologicallyactive agent.
 3. The device in claim 1, further comprising a pHsensitive coating.
 4. The device in claim 1, wherein the shape memorypolymer is biodegradable.
 5. The device of claim 1, wherein the shapememory polymer changes from the first form to the second form uponexposure to a stimulus.
 6. The device of claim 1 for gastric retention.7. The device of claim 1 for insertion into the uterus via the vagina.8. The device of claim 1 for insertion into the ureter.
 9. A method fortreating diseases and disorders of the gastrointestinal tract orurogenital tract comprising orally administering a composition to apatient, wherein the composition comprises a device comprising a shapememory polymer, and exposing the device to a stimulus which changes theform of the device.
 10. The method of claim 9, wherein the compositionis delivered to the stomach.
 11. The method of claim 9, wherein thecomposition is delivered to the esophagus.
 12. The method of claim 9,wherein the stimulus is selected from the group consisting of a changein temperature, a change in the pH, light, and water.
 13. The device ofclaim 5 wherein the stimulus is selected from the group consisting of achange in temperature, a change in the pH, light, and water.